NM_001005197.2:c.229A>G

Variant names:

• chr11-123906660-A-G
• rs570823925
• NM_001005197.2:c.229A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001005197.2(OR8D4):​c.229A>G​(p.Ile77Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I77F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: OR8D4 NM_001005197.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.386
• Publications: 0 publications found

Genes affected

OR8D4 (HGNC:14840): (olfactory receptor family 8 subfamily D member 4) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04577142).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005197.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR8D4	NM_001005197.2	MANE Select	c.229A>G	p.Ile77Val	missense	Exon 2 of 2	NP_001005197.1	Q8NGM9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR8D4	ENST00000641687.1	MANE Select	c.229A>G	p.Ile77Val	missense	Exon 2 of 2	ENSP00000493391.1	Q8NGM9
	OR8D4	ENST00000321355.3	TSL:6	c.229A>G	p.Ile77Val	missense	Exon 1 of 1	ENSP00000325381.2	Q8NGM9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461054 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726882

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111258

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.80
DEOGEN2	Benign	0.0021	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.54	N
PhyloP100		0.39
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.65	N
REVEL	Benign	0.041
Sift	Benign	0.22	T
Sift4G	Benign	0.24	T
Polyphen		0.012	B
Vest4		0.039
MutPred		0.43		Gain of catalytic residue at I77 (P = 0.0314)
MVP		0.11
MPC		0.015
ClinPred		0.12	T
GERP RS		-1.8
Varity_R		0.056
gMVP		0.023
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs570823925; hg19: chr11-123777367;